This invention relates to control of ocular development and, more particularly, to the treatment of the eye to control the development of myopia (commonly known as nearsightedness).
It has been estimated that about one of every four persons on earth suffers from myopia. About one-half or more of these cases are axial myopia, i.e., an elongation of the eye along the visual axis.
At birth, the human eye is about two-thirds adult size and is even at that size relatively short in the axial direction. As a consequence, young children tend to be farsighted. During childhood, as the eye grows, there is a compensatory fine tuning of the optical properties of the cornea and lens to the increasing ocular length. Often the entire process is virtually perfect such that no correction is needed for sharp vision of a distant object; the eye is emmetropic. When regulatory failure in this finely tuned process occurs, it usually goes toward a lengthened eye. As a result, distant images focus in front of the plane of the retina and axial myopia results. If, on the other hand, the regulatory failure leads to an eye whose ocular length is too short, near images would focus behind the plane of the retina and the result is hyperopia (commonly known as farsightedness).
Over the years, many theories have been put forth to explain the development of myopia, e.g., inheritance, excessive near work, and environmental influences such as hours of sunshine, diet, etc. From these theories many preventative measures have been proposed including spectacles, eye exercise, eye rest, cycloplegics, and other drug therapies. The clinical literature on the subject is both massive and inconclusive.
There is now substantial evidence to link the posterior part of the eye, specifically image quality at the retina, to the postnatal regulation of ocular growth. There is significant experience of myopia resulting in an eye that is subjected to retinal images of poor quality. Axial myopia can be experimentally induced, in either birds or primates, in an eye in which the retina is deprived of formed images, e.g., by suturing the eyelids or wearing an image-diffusing goggle. The experimental myopia induced in primates such as monkeys precisely mimics the common axial myopia of humans.
Thus, the phenomenon of an animal's vision process apparently contributes to the feedback mechanism by which postnatal ocular growth is normally regulated and refractive error is determined. This indicates that this mechanism is neural and likely originates in the retina.
Studies reported in Stone et al. (1988) Proc. Natl. Acad. Sci. 85: 257-260, revealed that there is an increase in retinal vasoactive intestinal peptide after eyelid fusion in primates. In all animals, the immunohistochemical reactivity of the retina for vasoactive intestinal peptide was much higher in the closed than in the open eyes.
In the application of R. A. Stone, A. M. Laties and P. M. Iuvone, U.S. application Ser. No. 342,942, filed Apr. 25, 1989, which is a continuation-in-part of Ser. No. 202,220, filed June 3, 1988, method of controlling the abnormal postnatal growth of the eye of a maturing animal was found which comprises controlling the presence of a neurochemical, by agonist therapy, which neurochemical is found to be changed under conditions during maturation leading to abnormal axial length. Therein it is disclosed that in experimental animals, such as chicks or monkeys, subjected to ocular image deprivation ordinarily leading to the development of myopia, the metabolism of certain retinal neurochemicals is altered leading to changes in retinal concentrations thereof. Specifically, retinal concentrations of dopamine were found to be reduced during such image deprivation and the ocular administration of a dopamine-related agent, e.g., apomorphine, a dopamine agonist, was found to inhibit or actually prevent the axial enlargement of the eye under conditions ordinarily leading to such enlargement.
In the application of A. M. Laties and R. A. Stone, U.S. application Ser. No. 369,293, filed June 21, 1989, is described a method of controlling the abnormal postnatal growth of the eye of a maturing animal by the administration of effective amounts of a muscarinic pharmacological agent known to be effective in brain neural tissue and/or neural ganglia, e.g., a muscarinic antagonist such as pirenzepine. Also described therein is the use of a cholinergic agonist such as carbamyl choline for inducing axial growth of the eye of a maturing animal.